Arthropod repellant

ABSTRACT

The present invention relates to compositions for repelling arthropods, these compositions being based on piperidine derivatives of the formula (I) ##STR1## in which R represents alkyl or alkoxy, together with fatty acids and/or fatty acid derivatives as synergists.

This application is a 371 of PCT/EP97/02138, filed on Apr. 25, 1997.

The present invention relates to compositions for repelling arthropods,these compositions being based on piperidine derivatives and fatty acidsand fatty acid derivatives as synergists.

It has been disclosed that certain piperidine derivatives can beemployed as agents for repelling insects and mites (cf. EP-A 0 281 908and EP-A 0 289 842). However, a considerable disadvantage of the knownrepellents is their long-term action, which is relatively short in somecases.

A considerable disadvantage of the known repellents is their long-termaction, which is relatively short in some cases.

The prolonged activity of certain repellents, for example Deet®, due toa combination with vegetable oils and/or fatty acids and/or their estershas also been disclosed (cf., for example, DE-A 38 42 232 and JP 042 44001). Again, the long-term action of these mixtures is not alwayssatisfactory.

It has been found that mixtures of piperidine derivatives of the formula(I) ##STR2## in which R represents alkyl or alkoxy

with fatty acids and/or fatty acid derivatives as synergists have goodarthropod-repellent properties.

The repellent action of the mixtures according to the invention isconsiderably more potent than that of the pure piperidine derivatives,the fatty acids causing not only an additive, but a synergistic,increase in activity.

The compositions according to the invention are therefore a valuableenrichment of the art.

Formula (I) provides a general definition of the piperidine derivatives.Preferred compounds are those in which R represents C₁ -C₄ -alkyl or C₁-C₄ -alkoxy. Especially preferred compounds are those in which Rrepresents C₃ -C₄ -alkyl or C₃ -C₄ -alkoxy.

Very especially preferred compounds of the formula (I) which can be usedaccording to the invention are the following: ##STR3##

The piperidine derivatives which can be used according to the inventionhave been disclosed (cf. EP-A 0 281 908 and EP-A 0 289 842).

Synergists which are suitable for the mixtures according to theinvention are preferably even-numbered, straight-chain higher fattyacids, in particular C₆ -C₁₈ -fatty acids, or their derivatives such as,in particular, fatty acid esters.

Synergists which may especially preferably be mentioned are caprylicacid (C₈) and capric acid (C₁₀) and their alkyl esters such as, inparticular, the methyl esters.

The fatty acids or their derivatives can be employed singly or in theform of variously composed mixtures of a variety of fatty acids/fattyacid derivatives.

It is also possible to employ substances which contain a mixture ofvarious fatty acids in the first place, such as, preferably, vegetableoils.

Examples which may be mentioned are: citronella oil, clove oil,patchouli oil, rapeseed oil, juniper oil or coconut oil.

The compositions of the inventive mixtures of compounds of formula (I)and fatty acids and/or fatty acid derivatives can vary within asubstantial range. Preferably the mixtures contain 1 to 90 percent perweight, more preferred 1 to 50 percent per weight and especiallypreferred 1 to 20 percent per weight of components of formula (I).

In a special embodiment, the mixtures according to the invention ofpiperidine derivatives of the formula (I) with fatty acids or fatty acidderivatives as synergists may also comprise other arthropod repellents.All repellents which can conventionally be used may be employed (cf.,for example, K. H. Buchel, Chemie der Pflanzenschutz-undSchadlingsbekampfungsmittel [Chemistry of Crop Protection Products andPesticides]; Editor: R. Wegler, Vol. 1, Springer Verlag BerlinHeidelberg New York, 1970, p. 487 et seq.).

Substances which are preferably used are repellent carboxamides,1,3-alkanediols, carboxylates, lactone derivatives and also β-alaninederivatives which are disubstituted on the nitrogen. Individual exampleswhich may be mentioned are: N,N-diethyl-3-methylbenzamide (Deet),N,N-diethylphenylacetamide (DEPA), 2-ethyl-hexane-1,3-diol (Rutgers612), dimethyl phthalate,1,1,4,5,6,7,8,8a-octahydro-3H-2-benzopyran-3-one and ethyl3-(N-n-butyl-N-acetyl)-aminopropionate.

The mixtures according to the invention can be used successfully forrepelling sucking and biting arthropods which are harmful or a nuisance,preferably insects, ticks and mites.

The sucking insects include essentially the mosquitoes (for exampleAedes aegypti, Aedes vexans, Culex quinquefasciatus, Culex tarsalis,Anopheles albimanus, Anopheles gambiae, Anopheles stephensi, Mansoniatitillans), moth gnats (for example Phlebotomus papatasii), gnats (forexample Culicoides furens), buffalo gnats (for example Simuliumdamnosum), biting flies (for example Stomoxys calcitrans), tsetse flies(for example Glossina morsitans morsitans), horse flies (for exampleTabanus nigrovittatus, Haematopota pluvialis, Chrysops caecutiens), trueflies (for example Musca domestica, Musca autumnalis, Muscavetustissima, Fannia canicularis), flesh-flies (for example Sarcophagacarnaria), myiasis-causing flies (for example Lucilia cuprina,Chrysomyia chloropyga, Hypoderma bovis, Hypoderma lineatum, Dermatobiahominis, Oestrus ovis, Gasterophilus intestinalis, Cochliomyiahominivorax), bugs (for example Cimex lectularius, Rhodnius prolixus,Triatoma infestans), lice (for example Pediculus humanis, Haematopinussuis, Damalina ovis), fleas (for example Pulex irritans, Xenopsyllacheopis, Ctenocephalides canis, Ctenocephalides felis) and sand fleas(Dermatophilus penetrans).

The biting insects include essentially cockroaches (for exampleBlattella germanica, Periplaneta americana, Blatta orientalis, Supellalongipalpa), beetles (for example Sitiophilus granarius, Tenebriomolitor, Dermestes lardarius, Stegobium paniceum, Anobium punctatum,Hylotrupes bajulus), termites (for example Reticulitermes lucifugus),ants (for example Lasius niger, Monomorium pharaonis), wasps (forexample Vespula germanica) and larvae of moths (for example Ephestiaelutella, Ephestia cautella, Plodia interpunctella, Hofmannophilapseudospretella, Tineola bisselliella, Tinea pellionella, Trichophagatapetzella).

The remaining arthropods include ticks (for example Ixodes ricinus,Argas reflexus, Ornithodorus moubata, Boophilius microplus, Amblyommahebraeum) and mites (for example Sarcoptes scabiei, Dermatophagoidespteronyssinus, Dermatophagoides farinae, Dermanyssus gallinae, Acarussiro).

The mixtures according to the invention, which can be employed undilutedor, preferably, diluted, may be employed in the formulationsconventionally used for repellents.

For use on humans or animals, these are solutions, emulsions, gels,ointments, pastes, soaps, shampoos, creams, powders, sticks, impregnatedsponges, micro-capsules, sprays or aerosols from spray cans.

A possible formulation for mixtures according to the inventionspecifically in the field of veterinary medicine is polymeric shapedarticles (for example ear tags, collars, medallions).

For use in or outside buildings, the mixtures according to the inventioncan be incorporated into granules, oil sprays, organic and water-basedconcentrates or slow-release formulations.

Moreover, the mixtures according to the invention may be employed invaporizer systems: The compounds are either located on a cellulosetablet resting on a plate which is heated electrically or by means of aflame, or they are in solution in a reservoir from which they arereleased into the atmosphere of the room by means of a heated wick.Instead of the cellulose tablet, it is also possible to use an aluminiumtrough, sealed with a membrane, which contains the compounds in the formof a gel.

Furthermore, the mixtures according to the invention may be formulatedas mosquito coils or candles, where burning makes the substancesevaporate from the burning site.

The products are prepared in a known manner by mixing or diluting themixtures according to the invention with solvents (for example xylene,chlorobenzenes, paraffins, methanol, ethanol, isopropanol, water),carriers (for example kaolins, clays, talc, chalk, highly-dispersesilica, silicates), emulsifiers (for example polyoxyethylene fatty acidesters, polyoxyethylene fatty alcohol ethers, alkylsulfonates,arylsulfonates) and dispersants (for example lignin-sulfate wasteliquors, methyl cellulose) or by incorporation in microcapsules (forexample based on gum arabic, gelatin, urea).

The mixtures according to the invention are employed in any desiredratio and can be used, in the formulations, as a mixture with each otheror else as a mixture with other known active compounds (for examplesunscreens). In general, the preparations comprise between 0.1 and 95%by weight, preferably between 0.5 and 90% by weight, of mixtureaccording to the invention.

To afford protection against the abovementioned arthropods, the mixturesaccording to the invention are either applied to the human or animalskin or hair, or coat, respectively, or used to treat items of clothingand other objects.

The mixtures according to the invention are also suitable as aconstituent of impregnants, for example for textile webs, curtains,items of clothing, packing materials, and for use in polishingmaterials, detergents and window cleaners.

The invention will be illustrated in greater detail by the followinggeneral examples for the preparations and the use of the mixturesaccording to the invention.

BRIEF DESCRIPTION OF THE DRAWINGS

The illustration of the invention in greater detail will make referenceto the drawings, wherein:

FIG. 1 is a drawing depicting a Y-olfactometer.

FIG. 2 is a heater unit used in the Y-olfactometer of FIG. 1.

FORMULATION EXAMPLE 1

A repellent in the form of a lotion for use on human or animal skin isprepared by mixing 20 parts of one of the mixtures according to theinvention, 1.5 parts of fragrance and 78.5 parts of isopropanol orethanol.

FORMULATION EXAMPLE 2

A repellent in the form of an aerosol for spraying onto the human oranimal skin is composed of 40% active compound solution (consisting of20 parts of one of the mixtures according to the invention, 1 part offragrance and 79 parts of isopropanol) and 60% of propane/butane (ratio15:85).

USE EXAMPLES

The following are employed in the use examples below:

a) Pyridine derivative of the formula (I): ##STR4## b) Synergist: C₈-fatty acid (caprylic acid) or

C₁₀ -fatty acid (caprinic acid) or

C₈ /C₁₀ -fatty acid mixture, ratio 1:1

EXAMPLE A

As a repellent on the skin

Method:

Gauze cages of dimensions 50×60×60 cm contain midge populations (Aedesaegypti) of approximately 5,000 specimens of all ages and both sexes.The animals are fed exclusively on sugar-water.

A guinea pig whose back has been shorn the previous day over an area of50 cm² and then treated with depilatory cream (cream was subsequentlyremoved with water) is held in place in a cage (box) in such a way thatonly the shorn area is accessible for the mites.

After the area has been treated with 0.4 ml of preparation (mixtureaccording to the invention in isopropanol) (using a pipette), the guineapig, including box, is placed into a cage containing the test animals.

Observation over 5 minutes reveals the number of midges which havebitten the guinea pig. The latter is then removed, and the test isrepeated after one hour. The experiment is carried out for not longerthan 9 hours, or until the activity ceases (>5 bites).

3 replications are carried out per preparation, and, after theexperiment has ended, the average is calculated for each evaluationtime.

If the activity ceases earlier in one replication, the last valuedetermined continues to be used for the evaluation times which followand is included in the calculation of the averages of the subsequentevaluation times.

The synergism is detected using S. R. Colby's formula; Weeds 15 20-22:##EQU1## E=expected duration of protection of the mixture according tothe invention

X=actual duration of protection of the pyridine derivative of theformula (I) alone

Y=actual duration of protection of the fatty acid(s) alone

If E is less than the actually observed duration of protection of themixture, then synergism is present.

Results:

Temperature: 25-27° C., relative atmospheric humidity: approx. 60%

                  TABLE 1                                                         ______________________________________                                        Compound of the formula (I-1) with                                            C.sub.8 /C.sub.10 -fatty acid mixture; E = 5.95 hours                                                             Duration                                  Prep-  Number of bites on the guinea pig after                                                                    of                                        aration                                                                              0 h   1 h   2 h 3 h 4 h 5 h 6 h 7 h 8 h  9 h protection                ______________________________________                                        1% (I-1)                                                                             0     0     0   2.0 4.7 5.3                  5 h                       1% C.sub.8 /C.sub.10                                                          1% (I-1)                                                                             0     0     0   1.0 4.0 4.0 4.0 4.3 4.0  5.7 9 h                       2% C.sub.8 /C.sub.10                                                          2% (I-1)                                                                             0     0.3   0.3 0   1.7 1.7 3.0 6.7          7 h                       1% C.sub.8 /C.sub.10                                                          2% (I-1)                                                                             0     0     0.3 0   0.7 1.3 3.3 4.3 4.3  5.3 9 h                       2% C.sub.8 /C.sub.10                                                          2% (I-1)                                                                             0.7   0     0.3 0.3 4.3 6.0                  5 h                       without                                                                       addition                                                                      2% C.sub.8 /C.sub.10                                                                 0.5   8.5                                    1 h                       alone                                                                         ______________________________________                                    

                  TABLE 2                                                         ______________________________________                                        Compound of the formula (I-1) with C.sub.8 -fatty acid;                       E = 5.00 hours                                                                                            Duration                                                  Number of bites on the guinea pig after                                                           of                                                Preparation                                                                             0 h   1 h   2 h  3 h 4 h 5 h 6 h  7 h protection                    ______________________________________                                        2% (I-1)  0     0.3   0.3  0.3 0.3 1.3 2.3  7.7 7 h                           1% C.sub.8                                                                    2% (I-1)  0     0     0    1.0 2.3 4.7 4.7  6.3 7 h                           2% C.sub.8                                                                    2% (I-1)  0     0     0.7  1.0 2.3 6.7          5 h                           without addition                                                              2% C.sub.8 alone                                                                        7.0                                   0 h                           ______________________________________                                    

                  TABLE 3                                                         ______________________________________                                        Compound of the formula (I-1) with C.sub.10 -fatty acid;                      E = 5.00 hours                                                                                            Duration                                                  Number of bites on the guinea pig after                                                           of                                                Preparation                                                                             0 h   1 h   2 h  3 h 4 h 5 h 6 h  7 h protection                    ______________________________________                                        2% (I-1)  0     0.3   0.3  1.0 3.3 4.7 6.3      6 h                           1% C.sub.10                                                                   2% (I-1)  0     0     0    0.3 1.0 3.7 3.7  8.3 7 h                           2% C.sub.10                                                                   2% (I-1)  0     0     0.3  2.0 4.7 6.0          5 h                           without                                                                       addition                                                                      2% C.sub.10                                                                             8.0                                   0 h                           alone                                                                         ______________________________________                                    

EXAMPLE B

As a repellent in vaporizer systems

Method

The experiments are carried out in a Y-olfactometer as shown in FIG. 1:

FIG. 1

1=Y-tube

2=current (20-30 cm/s)/temperature 27-29° C./rel. humidity 70-80%

3=fan

4=gauze

5=container (removable from Y-tube)

6=thermometer and detector for humidity

7=container K

8=container T

9=stimulation part

10=heater

11=water reservoir

12=compressed air

13=activated carbon

14=water supply

A container containing 20-30 midges (Aedes aegypti) which have beenlured into the container by hand from a cage is attached on theleft-hand side of the olfactometer as can be seen in FIG. 1(gauze-sealed). After the animals have been allowed to settle for 10minutes, the stimulation port of container T is equipped with a smallheater (plate temperature 110° C.) on which there are positioned, onfilter paper, a skin extract (source of attractant stimulation) or 0.1ml of preparation (mixture according to the invention in methanol)+skinextract (FIG. 2):

FIG. 2

1=cable

2=arrangement to be hung up in the olfactometer

3=fence

4=hotplate

F1=Filter disc with skin extract

F2A=Filter disc with preparation on hotplate

After 1 minute, the containers are closed, the heater is removed, andthe midges in the containers are counted.

The activity is calculated using the following formula: ##EQU2##

+100 denotes the highest attractant effect (all midges in container T),-100 means the highest repellent effect (all midges outside).

After the test, the midges are removed, and, after the olfactometer hasbeen run empty for 10 minutes, fresh midges are introduced, which areagain allowed to settle for 10 minutes.

A test series is started with skin extract, then the preparation+skinextract is tested, and finally again the skin extract.

The synergism is detected using the above-described formula of S. R.Colby; Weeds 15, 20-22.

Results:

Temperature: 26-28° C., relative atmospheric humidity: approx. 75%

                  TABLE 1                                                         ______________________________________                                        Compound of the formula (I-1) with C.sub.8 /C.sub.10 -fatty acid mixture;     E = -51.96                                                                    Preparation              Activity                                             ______________________________________                                                    only       skin extract                                                                            +73                                          1.0 mg (I-1)                                                                              +          skin extract                                                                            -73                                          1.0 mg C.sub.8 /C.sub.10                                                      1.0 mg (I-1)                                                                              +          skin extract                                                                            -16                                          without addition                                                              1.0 mg C.sub.8 /C.sub.10                                                                  +          skin extract                                                                            -31                                          alone                                                                                     only       skin extract                                                                            +93                                          ______________________________________                                    

                  TABLE 2                                                         ______________________________________                                        Compound of the formula (I-1) with C.sub.8 -fatty acid; E = +37.10            Preparation              Activity                                             ______________________________________                                                    only       skin extract                                                                            +87                                          1 mg (I-1)  +          skin extract                                                                            -22                                          1 mg C.sub.8                                                                  1 mg (I-1)  +          skin extract                                                                            +26                                          without addition                                                              1 mg C.sub.8                                                                              +          skin extract                                                                            +15                                          alone                                                                                     only       skin extract                                                                            +75                                          ______________________________________                                    

                  TABLE 3                                                         ______________________________________                                        Compound of the formula (I-1) with C.sub.10 -fatty acid; E = -24.32           Preparation              Activity                                             ______________________________________                                                    only       skin extract                                                                            +75                                          1 mg (I-1)  +          skin extract                                                                            -85                                          1 mg C.sub.10                                                                 1 mg (I-1)  +          skin extract                                                                            +16                                          without addition                                                              1 mg C.sub.10                                                                             +          skin extract                                                                            -48                                          alone                                                                                     only       skin extract                                                                            +73                                          ______________________________________                                    

What is claimed is:
 1. An arthropod repellent composition comprising acombination of at least one piperidine derivative of the formula (I):##STR5## in which R represents alkyl or alkoxy,and at least one fattyacid and/or fatty acid ester.
 2. The arthropod repellant compositionaccording to claim 1, wherein R in formula (I) represents C₁ -C₄ -alkylor C₁ -C₄ -alkoxy.
 3. The arthropod repellant composition according toclaim 1, which comprises at least one piperidine derivative of theformulae: ##STR6## and at least one fatty acid and/or fatty acid ester.4. The arthropod repellant composition according to claim 1, wherein thefatty acid and/or fatty acid ester is selected from the group consistingof even-numbered, straight-chain C₆ -C₁₈ fatty acids and their esters.5. The arthropod repellant composition according to claim 4, wherein thefatty acid and/or fatty acid ester is selected from the group consistingof caprylic acid (C₈), capric acid (C₁₀) and their alkyl esters.
 6. Thearthropod repellant composition according to claim 5, wherein the fattyacid ester is methyl caprate.
 7. The arthropod repellant compositionaccording to claim 1, wherein the fatty acid and/or fatty acid ester isa misture of fatty acids.
 8. The arthropod repellant compositionaccording to claim 1, wherein the fatty acid ester is in the form of atleast one vegetable oil.
 9. The arthropod repellant compositionaccording to claim 8, wherein the vegetable oil is selected from thegroup consisting of citronella oil, clove oil, patchouli oil, rapeseedoil and juniper oil.
 10. The arthropod repellant composition accordingto claim 1, wherein the combination of the piperidine derivative offormula (I) and the fatty acid and/or fatty acid ester comprises between0.1 and 95% by weight of the arthropod repellant composition.
 11. Aprocess for repelling arthropods, said process comprising applying tosaid arthropods or to an area from which it is desired to exclude saidarthropods an arthropod repelling effective amount of an arthropodrepellant composition according to any one of claims 1-10.